The intramolecular Diels-Alder reaction shows great promise for use in natural product synthesis owing to the fact that the reaction facilitates the construction of stereochemically complex bi- and poly-cyclic ring systems. Literature is cited in support of the suggestion that steric, conformational and electronic factors are sometimes more important than exo-endo considerations in determining the stereochemical outcome of the reaction. The interrelationships between these factors are not well understood. Consequently, fundamental studies of the reaction are proposed together with their application towards the total synthesis of medicinally important compounds such as the steroids, the pseudoguaianolides, and chlorothricolide, a macrolide antibiotic.